Published Online
on May 12, 2008

A more recent version of this article appeared on May 20, 2008

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Submitted on August 6, 2007
Accepted on February 11, 2008

Inhibition of Interleukin-1 by Anakinra Improves Vascular and Left Ventricular Function in Patients With Rheumatoid Arthritis

Ignatios Ikonomidis MD^*, John P. Lekakis MD, Maria Nikolaou MD, Ioannis Paraskevaidis MD, Ioanna Andreadou PhD, Theophania Kaplanoglou MD, Pelagia Katsimbri MD, Grigorios Skarantavos MD, Panayiotis N. Soucacos MD, and Dimitrios T. Kremastinos MD

From the 2nd Department of Cardiology (I.I., J.P.L., M.N., I.P., D.T.K.), and 1st Department of Orthopaedics (T.K., P.K., G.S., P.N.S.), Athens University, Attikon Hospital, and Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens (I.A.), Athens, Greece.

^* To whom correspondence should be addressed. E-mail: ignoik{at}otenet.gr.

Background—Interleukin-1 increases nitrooxidative stress. We investigated the effects of a human recombinant interleukin-1a receptor antagonist (anakinra) on nitrooxidative stress and vascular and left ventricular function.

Methods and Results—In an acute, double-blind trial, 23 patients with rheumatoid arthritis were randomized to receive a single injection of anakinra (150 mg SC) or placebo and, after 48 hours, the alternative treatment. At baseline and 3 hours after the injection, we assessed (1) coronary flow reserve, aortic distensibility, systolic and diastolic (Em) velocity of the mitral annulus, and E to Em ratio (E/Em) using echocardiography; (2) flow-mediated, endothelium-dependent dilation of the brachial artery; and (3) malondialdehyde, nitrotyrosine, interleukin-6, endothelin-1, and C-reactive protein. In a chronic, nonrandomized trial, 23 patients received anakinra and 19 received prednisolone for 30 days, after which all indices were reassessed. Compared with baseline, there was a greater reduction in malondialdehyde, nitrotyrosine, interleukin-6, and endothelin-1 and a greater increase in flow-mediated dilation, coronary flow reserve, aortic distensibility, systolic velocity of mitral annulus, and E/Em after anakinra than after placebo (malondialdehyde -25% versus 9%; nitrotyrosine -38% versus -11%; interleukin-6 -29% versus 0.9%; endothelin-1 -36% versus -11%; flow-mediated dilation 45% versus -9%; coronary flow reserve 29% versus 4%; and aortic distensibility 45% versus 2%; P<0.05 for all comparisons). After 30 days of treatment, the improvement in biomarkers and in vascular and left ventricular function was greater in the anakinra group than in the prednisolone group (P<0.05).

Conclusions—Interleukin-1 inhibition improves vascular and left ventricular function and is associated with reduction of nitrooxidative stress and endothelin.

Key words: interleukins • inflammation • endothelium • inhibitors • microcirculation

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Clinical Summaries
Circulation 2008 117: 2567-2569. [Extract] [Full Text]

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